Liquid chromatography systems have sophisticated computer-controlled pumps that deliver solvent and sample through chromatography columns that fractionate the sample into its constituent components. The fractionated sample then flows through one or more analytical instruments, such as light scattering, refractive index, UV absorption, electrophoretic mobility, and viscosity detectors, to characterize its physical properties. During the analysis, the flow system provides a constant volume flow rate while minimizing flow and pressure variations. Modern chromatography pumps routinely supply fluid at tens to hundreds of bar with variations of 0.1% or less. They achieve this level of performance by using a series of techniques including pressure feedback at the pump head or using nonlinear pump strokes that correct for the effect of solvent compressibility (see, for example, Agilent 1200 Series Quaternary Pump User Manual, Agilent Technologies, Inc., Santa Clara, Calif.). Despite these impressive specifications the analytical instrument signals often show small periodic fluctuations in their baseline, referred herein as pump pulses. Some analytical instruments are particularly sensitive to the corrupting effect of pump pulses, which can obscure the primary measurement.
The performance of online differential viscometers is often limited by their ability to distinguish between a chromatography peak that produces a small change in viscosity that manifests as a pressure drop across a capillary, and a pump pulse that mimics one. Although differential viscometers are particularly prone towards pump pulse pickup, they are by no means the only analytical instruments that are affected. Differential refractive detectors also commonly display pressure pulses in the solvent baselines. Light scattering and UV/VIS absorption detectors tend to be relatively insensitive to pump pulses, but even so there are examples in the literature, which show that they too can be affected.
Pump pulses typically are observed as a periodic oscillation in the baseline of whatever signal the analytical instrument is measuring. When seen, the usual remedy is to reduce them at the source, either by performing maintenance on the pump to replace pistons and valve seals, or by adding external pulse dampeners such as the FlatLine™ models produced by Analytical Scientific Instruments US (Richmond, Calif.). However even when the pump is operating correctly, there will always been be residual pressure pulses that can be transduced by the analytical instrument chain. The next step towards minimizing the effect of pump pulses is to design the analytical instruments to be as insensitive as possible to them, while retaining sensitivity to the physical effect they are intended to measure. There are a number of ways to design instruments to make them intrinsically less sensitivity to pump pulses, an example of which will be described below, but even after the pumps and the instrumentation have been optimized, the sensitivity of an instrument is often still limited by pump pulse pickup. It is a goal of this invention to correct the measured signals in software to eliminate the residual effects of pump pulses.